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https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#1
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28430183/neuroprotectin-d1-upregulates-iduna-expression-and-provides-protection-in-cellular-uncompensated-oxidative-stress-and-in-experimental-ischemic-stroke
#2
Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong, Nicolas G Bazan
Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28421533/changes-in-the-prefrontal-glutamatergic-and-parvalbumin-systems-of-mice-exposed-to-unpredictable-chronic-stress
#3
Ryan Shepard, Laurence Coutellier
The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known risk factor of mood disorders including anxiety and depression. Abnormalities in PFC functioning have been well described in humans displaying stress-induced depressive symptoms, and hypoactivity of the PFC is now recognized to be a key feature of the depressed brain. However, little is known about the causes and mechanisms leading to this altered prefrontal functional activity in the context of stress-related mood disorders. We previously showed that unpredictable chronic mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV), an activity-dependent calcium-binding albumin protein expressed in a specific subtype of GABAergic neurons, highlighting a potential mechanism through which chronic stress leads to hypofunction of the PFC...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28419969/neurotoxic-effects-of-silver-nanoparticles-and-the-protective-role-of-rutin
#4
Mona M Ahmed, Mohamed M A Hussein
The toxicological studies on silver nanoparticles (Ag-NPs) have become a hot topic over the past few decades due to their unique properties on the nanoscale and widespread in many commercial products that launched into the market recently. This study was undertaken to shed light on Ag-NPs toxicity on neurotransmitters with special emphasis on the impact of concurrent administration of rutin with Ag-NPs in the experimental rats. The oral administration of Ag-NPs in rats induced brain oxidative stress, significant alterations in neurotransmitters and amino acids...
April 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#5
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28414930/antipsychotics-promote-gabaergic-interneuron-genesis-in-the-adult-rat-brain-role-of-heat-shock-protein-production
#6
Hiroo Kaneta, Wataru Ukai, Hanako Tsujino, Kengo Furuse, Yoshiyasu Kigawa, Masaya Tayama, Takao Ishii, Eri Hashimoto, Chiaki Kawanishi
Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801...
March 10, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28412304/synergistic-effect-between-d-ap5-and-muscimol-in-the-nucleus-accumbens-shell-on-memory-consolidation-deficit-in-adult-male-wistar-rats-an-isobologram-analysis
#7
Mohammad Nasehi, Elaheh Ostadi, Fatemeh Khakpai, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
The nucleus accumbens (NAc) glutamatergic and GABAergic systems are involved in memory processes. This study was investigated the involvement of NAc shell GABAergic system on D-AP5 induced memory consolidation deficit. The elevated plus-maze (EPM) test-retest paradigm was employed to assess memory in adult male Wistar rats. The results indicated that post-training intra-NAc shell injection of bicuculline (GABAA receptor antagonist) did not alter emotional memory consolidation. However, post-training intra-NAc shell microinjection of muscimol (GABAA receptor agonist, 0...
April 12, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28412220/inflammation-induced-glua1-trafficking-and-membrane-insertion-of-ca-2-permeable-ampa-receptors-in-dorsal-horn-neurons-is-dependent-on-spinal-tumor-necrosis-factor-pi3-kinase-and-protein-kinase-a
#8
G Wigerblad, J R Huie, H Z Yin, M Leinders, R A Pritchard, F J Koehrn, W-H Xiao, G J Bennett, R L Huganir, A R Ferguson, J H Weiss, C I Svensson, L S Sorkin
Peripheral inflammation induces sensitization of nociceptive spinal cord neurons. Both spinal tumor necrosis factor (TNF) and neuronal membrane insertion of Ca(2+) permeable AMPA receptor (AMPAr) contribute to spinal sensitization and resultant pain behavior, molecular mechanisms connecting these two events have not been studied in detail. Intrathecal (i.t.) injection of TNF-blockers attenuated paw carrageenan-induced mechanical and thermal hypersensitivity. Levels of GluA1 and GluA4 from dorsal spinal membrane fractions increased in carrageenan-injected rats compared to controls...
April 12, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28411102/zl006-protects-spinal-cord-neurons-against-ischemia-induced-oxidative-stress-through-ampk-pgc-1%C3%AE-sirt3-pathway
#9
Shu-Guang Liu, Yun-Mei Wang, Yan-Jun Zhang, Xi-Jing He, Tao Ma, Wei Song, Yu-Min Zhang
Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28407141/sensory-deprivation-triggers-synaptic-and-intrinsic-plasticity-in-the-hippocampus
#10
Hila Milshtein-Parush, Samuel Frere, Limor Regev, Coren Lahav, Amit Benbenishty, Shamgar Ben-Eliyahu, Inbal Goshen, Inna Slutsky
Hippocampus, a temporal lobe structure involved in learning and memory, receives information from all sensory modalities. Despite extensive research on the role of sensory experience in cortical map plasticity, little is known about whether and how sensory experience regulates functioning of the hippocampal circuits. Here, we show that 9 ± 2 days of whisker deprivation during early mouse development depresses activity of CA3 pyramidal neurons by several principal mechanisms: decrease in release probability, increase in the fraction of silent synapses, and reduction in intrinsic excitability...
April 12, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28404824/glycolytic-inhibition-by-2-deoxy-d-glucose-abolishes-both-neuronal-and-network-bursts-in-an-in-vitro-seizure-model
#11
Li-Rong Shao, Carl E Stafstrom
Neuronal activity is energy demanding and coupled to cellular metabolism. In this study, we investigated the effects of glycolytic inhibition with 2-deoxy-D-glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and epileptiform network bursts in hippocampal slices. The effect of glycolytic inhibition on basal membrane properties was examined in hippocampal CA1 neurons, which are not ordinarily active spontaneously. Intracellular application of 2-DG did not significantly alter the membrane input resistance, action-potential threshold, firing pattern or input-output relationship of these neurons compared with simultaneously recorded neighboring neurons without intracellular 2-DG...
April 12, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28404816/pick1-ca-2-sensor-modulates-nmda-receptor-dependent-microrna-mediated-translational-repression-in-neurons
#12
Dipen Rajgor, Maria Fiuza, Gabrielle T Parkinson, Jonathan G Hanley
miRNAs are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex (RISC) proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlights their importance in synaptic plasticity. Previously we demonstrated a novel interaction between the major RISC component Argounaute-2 (Ago2) and the BAR-domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression...
April 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28404805/mutant-idh1-and-seizures-in-patients-with-glioma
#13
Hao Chen, Jonathon Judkins, Cheddhi Thomas, Meijing Wu, Laith Khoury, Carolina G Benjamin, Donato Pacione, John G Golfinos, Priya Kumthekar, Farhad Ghamsari, Li Chen, Pamela Lein, Dane M Chetkovich, Matija Snuderl, Craig Horbinski
OBJECTIVE: Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1(mut)) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1(mut) increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons. METHODS: Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1(mut) status...
April 12, 2017: Neurology
https://www.readbyqxmd.com/read/28404629/braf-signaling-principles-unveiled-by-large-scale-human-mutation-analysis-with-a-rapid-lentivirus-based-gene-replacement-method
#14
Chae-Seok Lim, Xi Kang, Vincent Mirabella, Huaye Zhang, Qian Bu, Yoichi Araki, Elizabeth T Hoang, Shiqiang Wang, Ying Shen, Sukwoo Choi, Bong-Kiun Kaang, Qiang Chang, Zhiping P Pang, Richard L Huganir, J Julius Zhu
Rapid advances in genetics are linking mutations on genes to diseases at an exponential rate, yet characterizing the gene mutation-cell behavior relationships essential for precision medicine remains a daunting task. More than 350 mutations on small GTPase BRaf are associated with various tumors, and ∼40 mutations are associated with the neurodevelopmental disorder cardio-facio-cutaneous syndrome (CFC). We developed a fast cost-effective lentivirus-based rapid gene replacement method to interrogate the physiopathology of BRaf and ∼50 disease-linked BRaf mutants, including all CFC-linked mutants...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28400714/deletion-of-trpc6-attenuates-nmda-receptor-mediated-ca-2-entry-and-ca-2-induced-neurotoxicity-following-cerebral-ischemia-and-oxygen-glucose-deprivation
#15
Jin Chen, Zhaozhong Li, Jeffery T Hatcher, Qing-Hui Chen, Li Chen, Robert D Wurster, Sic L Chan, Zixi Cheng
Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) and Ca(2+) and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca(2+) levels ([Ca(2+)] i ), we found that OGD induced a significant higher increase in glutamate-evoked Ca(2+) influx compared to untreated control and such an increase was reduced by TRPC6 deletion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28398653/the-noble-gas-xenon-provides-protection-and-trophic-stimulation-to-midbrain-dopamine-neurons
#16
Jérémie Lavaur, Déborah Le Nogue, Marc Lemaire, Jan Pype, Géraldine Farjot, Etienne C Hirsch, Patrick P Michel
Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In the present study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease (PD). Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28394782/decrease-of-growth-and-differentiation-factor-10-contributes-to-neuropathic-pain-through-n-methyl-d-aspartate-receptor-activation
#17
Long Jiang, Botao Tan, Sen Li, Li Wang, Liqiang Zheng, Yuan Liu, Zaiyun Long, Yamin Wu
Neuropathic pain is a chronic disease with hallmarks such as chronic allodynia and hyperalgesia. Previous studies have shown that the transforming growth factor-β superfamily acts as a protecting factor against neuropathic pain. In the current study, we found that growth and differentiation factor 10 (GDF10), which belongs to the transforming growth factor-β superfamily, is mainly expressed in the superficial layers of spinal dorsal horn neurons and it was dramatically downregulated after spinal nerve ligation and N-methyl-D-aspartate (NMDA) intrathecal infusion...
April 7, 2017: Neuroreport
https://www.readbyqxmd.com/read/28393079/tyrosine-phosphorylation-of-nr2b-contributes-to-chronic-migraines-via-increased-expression-of-cgrp-in-rats
#18
Xiping Liang, Sha Wang, Guangcheng Qin, Jingmei Xie, Ge Tan, Jiying Zhou, Devin W McBride, Lixue Chen
Tyrosine phosphorylation of NR2B (NR2B-pTyr), a subunit of the N-methyl-D-aspartate (NMDA) receptor, has been reported to develop central sensitization and persistent pain in the spine, but its effect in chronic migraines has not been examined. We hypothesized that tyrosine phosphorylation of NR2B contributes to chronic migraines (CM) through calcitonin gene-related peptide (CGRP) in rats. Ninety-four male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections. In a subset of animals, the time course and location of NR2B tyrosine phosphorylation were detected by western blot and immunofluorescence double staining...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28391945/particulate-matter-pm2-5-exposure-season-dependently-induces-neuronal-apoptosis-and-synaptic-injuries
#19
Minjun Chen, Ben Li, Nan Sang
Epidemiological studies have shown that particulate matter 2.5 (PM2.5) not only increases the incidence of cardiopulmonary illnesses but also relates to the development of neurodegenerative diseases. Considering that PM2.5 is highly heterogeneous with regional disparity and seasonal variation, we investigated whether PM2.5 exposure induced neuronal apoptosis and synaptic injuries in a season-dependent manner. The results indicated that PM2.5 altered the expression of apoptosis-related proteins (mainly bax and bcl-2), activated caspase-3 and caused neuronal apoptosis...
April 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28391013/p35-hemizygosity-activates-akt-but-does-not-improve-motor-function-in-the-yac128-mouse-model-of-huntington-s-disease
#20
Kevin H J Park, Sonia Franciosi, Kristina Parrant, Ge Lu, Blair R Leavitt
Huntington's disease (HD) is a hereditary neurodegenerative disorder resulting from N-terminal polyglutamine expansion in the huntingtin protein. A relatively selective and early loss of medium spiny neurons in the striatum is a hallmark of HD neuropathology. Although the exact mechanism of mutant huntingtin-mediated neurodegeneration is unclear, recent evidence suggests that NMDA-receptor-mediated excitotoxicity is involved. Our previously published findings show that decreasing levels of the cdk5 activators, p35 and p25, reduces NMDA receptor-mediated excitotoxicity in striatal neurons in vivo...
April 6, 2017: Neuroscience
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